The present invention relates generally to materials for making medical grade products and more specifically to a moisture-barrier film product which may be used to manufacture articles such as plastic containers and medical tubing.
In the medical field, where beneficial agents are collected, processed and stored in containers, transported, and ultimately delivered through tubes by infusion to patients to achieve therapeutic effects, materials which are used to fabricate the containers must have a unique combination of properties. For example, in order to visually inspect solutions for particulate contaminants, the container must be optically transparent. To infuse a solution from a container by collapsing the container walls, without introducing air into the container, the material which forms the walls must be sufficiently flexible. The material must be functional over a wide range of temperatures. The material must function at low temperatures by maintaining its flexibility and toughness because some solutions, for example, certain premixed drug solutions are stored and transported in containers at temperatures such as xe2x88x9225 to xe2x88x9230xc2x0 C. to minimize the drug degradation. The material must also be functional at high temperatures to withstand the heat of sterilization; a process which most medical packages and nutritional products are subjected to prior to shipment. The sterilization process usually includes exposing the container to steam at temperatures typically 121xc2x0 C. and at elevated pressures. Thus, the material needs to withstand the temperature and pressures without significant distortions (xe2x80x9cheat distortion resistancexe2x80x9d).
For ease of manufacture into useful articles, it is desirable that the material be sealable using radio frequency (xe2x80x9cRFxe2x80x9d) generally at about 27.12 MHz. Therefore, the material should possess sufficient dielectric loss properties to convert the RF energy to thermal energy.
A further requirement is to minimize the environmental impact upon the disposal of the article fabricated from the material after its intended use. For those articles that are disposed of in landfills, it is desirable to use as little material as possible and avoid the incorporation of low molecular weight leachable components to construct the article. Thus, the material should be light weight and have good mechanical strength. Further benefits are realized by using a material which may be recycled by thermoplastically reprocessing the post-consumer article into other useful articles.
For those containers which are disposed of through incineration, it is necessary to use a material which helps to eliminate the dangers of biological hazards, and to minimize or eliminate entirely the formation of inorganic acids which are environmentally harmful, irritating, and corrosive, or other products which are harmful, irritating, or otherwise objectionable upon incineration.
It is also desirable that the material be free from or have a low content of low molecular weight additives such as plasticizers, stabilizers and the like.
Traditional flexible polyvinyl chloride materials meets a number of, and in some cases, most of the above-mentioned requirements. Polyvinyl chloride (xe2x80x9cPVCxe2x80x9d) also offers the distinct advantage of being one of the most cost effective materials for constructing devices which meet the above requirements. However, PVC may generate objectionable amounts of hydrogen chloride (or hydrochloric acid when contacted with water) upon incineration, causing corrosion of the incinerator. PVC sometimes contains plasticizers which may leach into drugs or biological fluids or tissues that come in contact with PVC formulations. Thus, many materials have been devised to replace PVC. However, most alternate materials are too expensive to implement and still do not meet all of the above requirements.
For certain medical products it may be necessary to provide a barrier against the transmission of water to provide a low water vapor transmission rate (WVTR). For example, for a 50 ml flexible diluent container associated with medical reconstitution devices it is desirable that the container be capable of being left outside of an overpouch or overwrap material for a 12 month period without losing 8% of its diluent content to evaporation through the film. While the barrier to water vapor transmission can be enhanced by increasing the thickness of layers that resists water vapor transmission, such an increase in thickness of these barrier materials can render the container too rigid to collapse upon draining or make the container too rigid to easily perform a drug reconstitution procedure.
There have been many attempts to develop a film material to replace PVC, but most attempts have been unsuccessful for one reason or another. For example, in U.S. Pat. No. 4,966,795 which discloses multi-layer film compositions capable of withstanding the steam sterilization, cannot be welded by radio frequency dielectric heating thus cannot be assembled by this rapid, low costs, reliable and practical process. European Application No. EP 0 310 143 A1 discloses multilayer films that meet most of the requirements, and can be RF welded. However, components of the disclosed film are cross-linked by radiation and, therefore, cannot be recycled by the standard thermoplastic processing methods. In addition, due to the irradiation step, appreciable amounts of acetic acid is liberated and trapped in the material. Upon steam sterilization, the acetic acid migrates into the packaging contents as a contaminant and by altering the pH of the contents acts as a potential chemical reactant to the contents or as a catalyst to the degradation of the contents.
The main objective of the present invention is the creation of thermoplastic materials which are, overall, superior to those materials, of which we are aware, which have been heretofore known to the art or have been commercially used or marketed. The properties of such materials includes flexibility, extensibility, and strain recoverability, not just at room temperatures, but through a wide range of ambient and refrigerated temperatures. The material should be steam sterilizable at temperatures typically at 121xc2x0 C. or slightly above or below. The material should be capable of being subjected to significant strains without exhibiting strain whitening, which can indicate a physical and a cosmetic defect. A further objective is that the material be capable of assembly by the RF methods. Another objective is that the material be substantially free of low molecular weight leachable additives, and be capable of safe disposal by incineration without the generation of significant amounts of corrosive inorganic acids. Another objective is that the material be recyclable by standard thermoplastic processing methods after use. It is also desirable that the material incorporate reground scrap material recovered during the manufacturing process to save material costs and reduce manufacturing waste. It is also desirable that the material have high barrier to water vapor transmission so that the material may be fabricated into fluid containers that do not require the use of an overpouch or overwrap material. It is also desirable that the material not be oriented as oriented films may shrink when subjected to heat. Finally, the material should serve as a cost effective alternative to various PVC formulations currently being used for medical devices.
The present invention is provided to solve these and other problems.
In accordance with the present invention certain multiple layer polymer based structures are disclosed. The films may be fabricated into medical grade articles such as diluent containers for reconstitution devices.
It is an object of the present invention to prepare a multi-layered film having the following physical properties: (1) a mechanical modulus less than 150,000 psi and more preferably less than 120,000 psi when measured in accordance with ASTM D-882; (2) a content of elemental halogens less than 5 0.1%, and more preferably less than 0.01%, (3) a low molecular weight water soluble fraction less than 0.1%, and more preferably less than 0.005%; (4) a maximum dielectric loss between 1 and 60 MHz and between the temperature range of 25-250xc2x0 C. greater than or equal to 0.05 and more preferably greater than or equal to 0.1; (5) an autoclave resistance measured by sample creep at 121xc2x0 C. under 27 psi loading is less than or equal to 60% and more preferably less than or equal to 20%; (6) there is no strain whitening after being strained at moderate speeds of about 20 inches per minute at about 100% elongation and the presence of strain whitening is noted or the lack thereof; (7) has a water vapor transmission rate for a water filled 50 ml container of less than 8%, more preferably less than 7% and most preferably less than 6% by weight when left outside an overpouch for a 12 month period and more preferably a 14 month period and (8) is not oriented.
The present invention provides a multiple layer thermoplastic structure suitable for manufacturing medical products satisfying the above-mentioned physical property requirements. The structure has a skin layer and a radio frequency susceptible layer. The skin layer is selected from the group consisting of polypropylene, ethylene homopolymers having a density from 0.930 g/cc-0.960 g/cc and blends of ethylene homopolymers and ethylene xcex1-olefin copolymers having a density less than about 0.930 g/cc. The radio frequency susceptible layer is adhered to the skin layer and has a dielectric loss greater than 0.05 at 1-60 MHz and at temperatures of ambient to 250xc2x0 C. The radio frequency susceptible layer comprises, in a preferred form of the invention, a four component blend. The first component is a first polyolefin selected from the group consisting of polypropylene and polypropylene copolymers. The second component is a second polyolefin selected from the group consisting of ethylene copolymers, ethylene and xcex1-olefin copolymers, ultra-low density polyethylene, polybutene, and butene ethylene copolymers. The third component is a radio frequency susceptible polymer selected from the group consisting of ethylene copolymers having 50-85% ethylene content with comonomers selected from a first group consisting of acrylic acid, methacrylic acid, ester derivatives of acrylic acid with alcohols having 1-10 carbons, ester derivatives of methacrylic acid with alcohols having 1-10 carbons, vinyl acetate, carbon monoxide and vinyl alcohol. The RF susceptible polymer may also be selected from a second group consisting of homopolymers and copolymers containing segments of urethane, esters, ureas, imides, sulfones, and amides. These functionalities may constitute between 5-100% of the RF susceptible polymer. The fourth component of the radio frequency susceptible layer is a compatibilizing agent of a styrene and hydrocarbon copolymer.
The present invention further provides intermediate layers to provide additional physical properties such as enhanced lower temperature performance as will be discussed in greater detail below. Also, the present invention provides using a three-component radio frequency susceptible layer.
Additional features and advantages of the present invention are described in, and will be apparent from, the drawing and the detailed description of the presently preferred embodiments.